Retrospective multicenter registry for endovascular treatment with newer devices in over 25‐cm femoropopliteal artery disease: A retrospective observational study

Abstract Background and Aims Endovascular therapy (EVT) is recommended in femoropopliteal (FP) lesions shorter than 25 cm by current guidelines; however, diffuse FP lesions remains challenging for EVT. The aim of this study was to investigate the efficacy of EVT with the latest devices for FP lesions longer than 25 cm. Methods This retrospective multicenter registry analyzed patients presented peripheral artery disease (PAD) having FP lesions longer than 25 cm who underwent EVT using the latest devices between 2017 and 2021. The primary outcome was restenosis 1 year after EVT. Results The present study enrolled a total of 504 PAD patients with 614 lesions undergoing EVT for diffuse FP lesions. The Kaplan–Meier analysis showed that the rates of freedom from restenosis and clinically‐driven target lesion revascularization were 79.3% and 82.4% 1 year after EVT, respectively. The multivariate Cox proportional hazards regression analysis showed that clinical features associated independently with restenosis risk were cilostazol use (adjusted hazard ratio, 0.49 [0.32–0.74]; p = 0.001), reference vessel diameter (RVD) (0.72 [0.58–0.89] per 1‐mm increase; p = 0.002), and P3 segment involvement (2.08 [1.33–3.26]; p = 0.001). The Kaplan–Meier analysis was conducted to compare the primary patency between cases with and without a small RVD, P3 involvement, and/or lack of cilostazol; any risk factors were related to a worse primary patency rate, compared with cases without risk factors. Conclusion In the current EVT era, the primary patency at 1 year was acceptable at 79.3% in patients with FP lesions longer than 25 cm. A small vessel and P3 segment involvement might be associated with a poor 1‐year patency rate after EVT, whereas cilostazol administration might contribute to reducing restenosis.


| INTRODUCTION
Recently, the evolution of endovascular treatment (EVT) devices aimed at reducing reintervention rates in femoropopliteal (FP) lesions, [1][2][3] and the European Society of Cardiology guidelines published in 2017 recommended EVT for FP lesions shorter than 25 cm as class I indication. 4 However, the prevalence of peripheral artery disease (PAD) is largely increasing worldwide because of aging patient population and diabetes pandemic. 5,6 Patients with symptomatic PAD have had more complex FP lesions such as chronic total occlusion (CTO), severe calcification, and diffuse lesions.
The guideline also recommends bypass surgery (BSX) using a saphenous vein graft as the first-choice treatment in patients with complex FP lesions, whereas suggested EVT for patients unsuitable for BSX with diffuse FP lesions, especially those longer than 25 cm (class IIb indication). 4 However, aging and presence of multiple comorbidities make BSX difficult in such patients. Therefore, in daily practice, EVT is often chosen to treat patients with both complex FP lesions and several comorbidities.
The aim of this study was to evaluate the safety and efficacy of the contemporary EVT using the latest devices in patients with symptomatic PAD having FP lesions longer than 25 cm in clinical practice. In addition, several studies indicated that medical treatment might be helpful to keep patency after revascularization such as antiplatelet therapy, cilostazol and oral anti-coagulation; therefore, anti-thrombotic therapies can play an important role in the current EVT era. [7][8][9] We investigated the associated factors to improve the vessel patency, which included patent and lesion background, EVT devices and medical treatment.

| Procedures
Following local anesthesia, a 5.0-to 7.0-French guiding sheath was inserted into a common femoral artery. In CTO lesions, the F I G U R E 1 Study flow chart. DCB, drug-coated balloon; DES, drug-eluting stent; EVT, endovascular therapy; IWS, interwoven nitinol stent; SG, stent-graft. wire-crossing technique was dependent on the discretion of each operator. The bidirectional approach was performed as needed. The types of finalized devices were also dependent on decision of operators at each institution. Since atherectomy and intravascular lithotripsy devices were not commercially available in our country during the study period, these devices were not used.

| Antithrombotic treatment
Dual antiplatelet therapy (DAPT; aspirin with clopidogrel or prasugrel) was prescribed for at least 1 week before the EVT and continued at least 1 month. 11 When patients had bleeding complications or high bleeding risks, single antiplatelet therapy (SAPT) could be allowed. 4 Subsequent prescription of the antiplatelet therapy was at the discretion of each treating physician. Oral anticoagulation was prescribed in patients with deep vein thrombosis, atrial fibrillation or heart valve implantation. In patients with oral anticoagulation, additional SAPT was recommended before and after the EVT. 4

| Study definition
This study included patients with FP lesions longer than 25 cm.
Procedural success was defined as residual stenosis less than 50%.
The primary outcome was primary patency within 1 year, defined as the absence of both restenosis and revascularization of the treated lesion. Restenosis was defined as a peak systolic velocity ratio of over 2.4 measured using duplex ultrasound, >50% diameter stenosis or occlusion by follow-up angiography. 12 The secondary outcomes included overall survival (freedom from all-cause mortality), limb salvage (freedom from major amputation), and freedom from clinically-driven target lesion revascularization (CD-TLR). Color Doppler ultrasonography was routinely performed at 6 and 12 months after EVT to assess arterial patency, as recommended by the reports from the Society for Vascular Surgery. 13 CD-TLR referred to any revascularization procedures for significant restenosis and/or reocclusion within 1 year after EVT, as identified by duplex ultrasonography or angiography, with recurrent symptoms.
The Peripheral Arterial Calcium Scoring System was used to categorize the severity of lesion calcification. 14

| RESULTS
The clinical characteristics are summarized in  (interquartile range), restenosis was detected in 135 cases. Figure 3 shows the Kaplan-Meier analysis of freedom from restenosis and Indeed, cases with P3 segment involvement and a small RVD had a higher risk of restenosis regardless of cilostazol use ( Figure 4). By  between SG and IWS (p = 0.65), respectively. Table 3 summarizes the rate of periprocedural complications and 12-month clinical outcomes.

| STUDY LIMITATIONS
The present study has several limitations. First, this study was nonrandomized and retrospective. This study was also an exploratory analysis, and future pre-specified studies would be needed to validate the present findings. Second, the EVT devices were selected according to discretion of each operator without pre-established protocol, which might cause selection bias. Third, patient/lesion information, and angiographic findings were not evaluated by an external core laboratory. Forth, DAPT continued at least 1 month after EVT in this study; however, the accurate duration of antithrombotic treatment was unknown.

| CONCLUSIONS
The current EVT might show the acceptable 1-year primary patency rate at 79.3% in patients with FP lesions longer than 25 cm. A small vessel and P3 segment involvement might be associated with a poor F I G U R E 4 Kaplan−Meier estimates of freedom from restenosis by lesion risk factors in a population with (A) and without cilostazol use (B). Lesion risk factors for restenosis were P3 involvement and reference vessel diameter < 5 mm (see Table 2). Dotted lines represent 95% confidence intervals.